title: Brain connectivity abnormalities predating the onset of psychosis: correlation with the effect of medication.
abstract: OBJECTIVE
  Brain imaging studies have identified robust changes in brain structure and function during the development of psychosis, but the contribution of abnormal brain connectivity to the onset of psychosis is unclear. Furthermore, antipsychotic treatment can modulate brain activity and functional connectivity during cognitive tasks.
  
  
  OBJECTIVE
  To investigate whether dysfunctional brain connectivity during working memory (WM) predates the onset of psychosis and whether connectivity parameters are related to antipsychotic treatment.
  
  
  METHODS
  Dynamic causal modeling study of functional magnetic resonance imaging data.
  
  
  METHODS
  Participants were recruited from the specialized clinic for the early detection of psychosis at the Department of Psychiatry, University of Basel, Basel, Switzerland.
  
  
  METHODS
  Seventeen participants with an at-risk mental state (mean [SD] age, 25.24 [6.3] years), 21 individuals with first-episode psychosis (mean [SD] age, 28.57 [7.2] years), and 20 healthy controls (mean [SD] age, 26.5 [4] years).
  
  
  METHODS
  Functional magnetic resonance imaging data were recorded while participants performed an N-back WM task. Functional interactions among brain regions involved in WM, in particular between frontal and parietal brain regions, were characterized using dynamic causal modeling. Bayesian model selection was performed to evaluate the likelihood of alternative WM network architectures across groups, whereas bayesian model averaging was used to examine group differences in connection strengths.
  
  
  RESULTS
  We observed a progressive reduction in WM-induced modulation of connectivity from the middle frontal gyrus to the superior parietal lobule in the right hemisphere in healthy controls, at-risk mental state participants, and first-episode psychosis patients. Notably, the abnormal modulation of connectivity in first-episode psychosis patients was normalized by treatment with antipsychotics.
  
  
  CONCLUSIONS
  Our findings suggest that the vulnerability to psychosis is associated with a progressive failure of functional integration of brain regions involved in WM processes, including visual encoding and rule updating, and that treatment with antipsychotics may have the potential to counteract this.
authors.affiliation: Department of Psychiatry, University of Basel, Basel, Switzerland2Medical Image Analysis Centre, University Hospital Basel, Basel, Switzerland.
authors.forename: André
authors.initials: A
authors.lastname: Schmidt
authors.forename: Renata
authors.initials: R
authors.lastname: Smieskova
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Aston
authors.forename: Andor
authors.initials: A
authors.lastname: Simon
authors.forename: Paul
authors.initials: P
authors.lastname: Allen
authors.forename: Paolo
authors.initials: P
authors.lastname: Fusar-Poli
authors.forename: Philip K
authors.initials: PK
authors.lastname: McGuire
authors.forename: Anita
authors.initials: A
authors.lastname: Riecher-Rössler
authors.forename: Klaas E
authors.initials: KE
authors.lastname: Stephan
authors.forename: Stefan
authors.initials: S
authors.lastname: Borgwardt
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D001931:Brain Mapping / Q000295:instrumentation / Q000379:methods; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D009483:Neuropsychological Tests; D011618:Psychotic Disorders / Q000188:drug therapy / Q000503:physiopathology*; D013557:Switzerland; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents